Efficacy of oral DMSA and intravenous EDTA in chelation of toxic metals and improvement of the number of stem/ progenitor cells in circulation

Metal toxicity represents a significant public health concern and contributes to many toxic metal-exposure related diseases. In particular, toxic metals promote the oxidative stress in stem cells and endothelial progenitor cells (EPCs). EPCs that are presented in peripheral blood function to replenish aging damaged endothelial cells and play important role in the maintenance of vasculature and neovascularization. Given the links between oxidative injury, endothelial cell dysfunction and vascular disease, we focused our investigation on the response of CD34-positive cells to chelation by DMSA. In addition, we compared the effectiveness of DMSA and EDTA in the chelation of toxic metals and the excretion of essential metals. The data were compared for 160 subjects after oral DMSA (500mg) chelation and 250 subjects after intravenous EDTA (1g-3g) chelation. Our in vitro experiments were designed to compare the intrinsic toxicity of two antidotes and their effectiveness in lead chelation. One of the important results of our study shows that the removal of toxic metals improves the number of stem/progenitor cells in circulation. After a series of five DMSA treatments, the number of CD34+ cells in circulation was increased on 50%160% (p<0.05). Our in vitro experiments demonstrated that toxic metals (lead and mercury) inhibit mesenchymal stem cell metabolism and proliferation, and that stem cells are more sensitive to these metals than differentiated cells. In comparison with EDTA, DMSA was more effective in the extraction of lead, but treatment by this antidote resulted in a very high excretion of copper (55 folds). Clearance of essential metals during chelation by 1g-3g of EDTA was increased over twenty-fold for zinc and manganese. In summary, we suggest that chelation therapy shows promise in repairing metal toxicity damage and restoring circulating stem cells.